Nektar Therapeutics announced that the first patient has been enrolled in a Phase 2 clinical study of NKTR-181, a new, first-of-its-kind, opioid analgesic candidate. NKTR-181 is a novel mu-opioid agonist molecule designed to have a slow rate of entry into the brain to reduce the attractiveness of the molecule as a target of abuse and to reduce other CNS-mediated side effects, such as sedation and respiratory depression. The Phase 2 study will utilize a double-blind, placebo-controlled, randomized withdrawal study design to assess the efficacy, safety and tolerability of NKTR-181 in patients with moderate to severe chronic pain from osteoarthritis of the knee. Approximately 200 patients will be randomized to receive either NKTR-181 or placebo in the study.
“NKTR-181 exhibited highly differentiated properties in its Phase 1 development, which include slow penetration across the blood-brain barrier into the CNS. This slow rate of entry may allow us to effectively address pain while reducing some of the most troubling opioid CNS effects such as euphoria, sedation, and respiratory depression. NKTR-181 represents a potential paradigm shift in the way we think about opioid analgesia,” said Jeffrey Gudin, MD, Director of Pain Management and Palliative Care, Englewood Hospital & Medical Center and Clinical Instructor of Anesthesiology at Mt. Sinai School of Medicine.
NKTR-181 is an NCE (new chemical entity) which was created using Nektar’s proprietary small molecule polymer conjugate technology and its potential differentiating properties are inherent to the design of the new molecule. As a new molecular structure, NTKR-181 does not rely on a formulation approach, which is a common method that has been used with opioid drugs in order to attempt to block their conversion into abusable forms of an opioid. Phase 1 studies demonstrated that NKTR-181 produced sustained and dose-dependent analgesic responses in healthy volunteers, a slower rate of CNS entry as measured by pupillometry, or contraction of the pupils, and an excellent tolerability profile. NKTR-181’s Phase 1 clinical development program evaluated the molecule in approximately 180 healthy volunteers.
“As a new mu-opioid analgesic molecule, NKTR-181 has the potential to transform the treatment of chronic pain by using a molecular approach to reduce the risk of traditional opioid therapy while preserving its analgesic benefit,” said Robert Medve, MD, the company’s Senior Vice President and Chief Medical Officer. “We are excited to be advancing this molecule into Phase 2 testing in chronic pain patients.”
The NKTR-181 Phase 2 study uses a randomized withdrawal design, which includes a baseline period and a drug titration period followed by a randomized, placebo-controlled, double-blind phase of the study. The primary endpoint of the study will be the average change in a patient’s pain score from baseline to the end of the double-blind, randomized treatment period. The study will enroll opioid-naive patients with osteoarthritis of the knee who are not getting adequate pain relief from their current non-opioid pain medication. Patients who qualify during the baseline period will enter a titration phase, during which they will be titrated on NKTR-181 tablets administered orally twice-daily until a dose is reached that provides a reduction of at least 20% in the patient’s pain score as compared to the patient’s own baseline. Patients that achieve this level of analgesia will then be randomized on a 1:1 basis to either continue to receive their analgesic dose of NKTR-181 or to receive placebo for up to 25 days. Secondary endpoints of the study include quality-of-life assessment, sleep and motor activity scoring, as well as tolerability endpoints.
The company is also planning a separate human abuse liability study for NKTR-181 as part of Phase 2 development for the compound. This study will measure liking scores for NKTR-181 as compared to an active opioid in approximately 20 recreational drug users.
Date: July 24, 2012
Source: Nektar Therapeutics https://www.nektar.com
Filed Under: Drug Discovery
